The goal of this research proposal is to compare several immunological adjuvant in the human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) vaccine program that is being undertaken by the Cooperative Group for AIDS Research and Vaccinology at the University of California, Davis. The SIV rhesus model system will help guide the development and testing of HIV vaccine materials. Inactivated whole virus will be the starting immunogen. HIV and SIV antigens produced in genetically engineered expression systems will also be evaluated. Adjuvants to be tested include alum, incomplete Freund's adjuvant, muramyl dipeptide and liposomes. The immune potentiating effects in small animals and rhesus monkeys of various vaccine-adjuvant formulations will be measured by appropriate assays for humoral and cellular immunity and the virus antigens to which these responses, are directed will be determined. Toxicity and adverse side-effects will also be evaluated. Rhesus monkeys immunized with candidate SIV vaccine-adjuvant combinations will be challenged with live SIV to test for efficacy with respect to preventing infection and pathogenesis. The information gathered on immune responses in unexposed monkeys in this proposal will be used in future studies to design immunotherapeutic approaches in SIV carriers with the aim of preventing of limiting disease. These investigations in sub- human primates will lay the basis for developing effective HIV vaccines for AIDS immunoprophylaxis and immunotherapy.